Double-strand DNA breakages occur frequently during DNA repair and are produced by ionizing radiation and certain chemicals [Haber, J. E., Trends Biochem. Sci., 24, 271–275 (1999)]. A single unrepaired double-strand DNA breakage is believed to cause cell death in yeast and vertebrate cells [Bennett, C. B. et al., Proc. Natl. Acad. Sci. USA, 90, 5613–5617; Huang, L. C. et al., Proc. Natl. Acad. Sci. USA, 93, 4827–4832 (1996)].
In yeast, homologous recombination repair is a major DNA breakage repair pathway. The above-mentioned homologous recombination repair pathway has been conserved from yeast to human [Shinohara, A. et al., Nat. Genet., 4, 239–243 (1993); Siede, W. et al., Genetics, 142, 91–102 (1996); Boulton, S. J. et al., Nucleic Acids Res., 24, 4639–4648 (1996a); Boulton, S. J. et al., EMBO J., 15, 5093–5103 (1996b); Bezzubova, O. Y. et al., Cell, 89, 185–193 (1997); Essers, J. et al., Cell, 89, 195–204 (1997); Thompson, L. H. et al., Biochimie, 81, 87–105 (1999)].
Presently, the analysis of radiosensitive yeast mutants has revealed numbers of key genes involved in the homologous recombination repair. The genes include, for instance, the Rad52 epistasis group and the like [Shinohara, A. et al., Trends Biochem. Sci., 20, 387–391 (1995); Baumann, P. et al., Trends Biochem. Sci., 23, 247–251; Kanaar, R. et al., Trends Cell Biol., 8, 483–489 (1998)].
Among the members of the RAD52 epistasis group, the structure and function of Rad51 have been conserved to a remarkable degree among all eukaryotes. The above-mentioned Rad51 structurally and functionally resembles Escherichia coli recombination protein RecA [reviewed in Kowalczykowski, S. C. et al., Experientia, 50, 204–15 (1994)]. Lethality of Rad51-deficient cells [Tsuzuki. T et al., Proc. Natl. Acad. Sci. USA, 93, 6236–6240 (1996); Lim, D. S. et al., Mol. Cell Biol., 16, 7133–7143 (1996); Sonoda. E. et al., EMBO. J., 17, 598–608 (1998)] has suggested that Rad51 plays a central role in the homologous recombination repair in vertebrate cells [Bezzubova, O. Y. et al., Cell, 89, 185–193 (1997); the above-mentioned Essers et al. (1997); Rijkers, T. et al., Mol. Cell Biol., 18, 6423–6429 (1998); Yamaguchi-Iwai, Y. et al., Mol. Cell. Biol., 18, 6430–6435 (1998)].
However, many of the detailed functions and roles for other Rad52 epistasis groups are yet unrevealed at the current situation.